methionine

A sulfur-containing essential amino acid, C₅H₁₁NO₂S, obtained from various proteins or prepared synthetically and used as a dietary supplement and in pharmaceuticals.

[ME(TH)- + THION- + -INE².]

An essential amino acid; one of the three containing sulphur; cystine and cysteine are the other two. Cystine and cysteine are not essential, but can only be made from methionine, and therefore the requirement for methionine is lower if there is an adequate intake of cyst (e)ine.

An essential sulphur-containing amino acid. All meats contain methionine. For vegetarians, grains and soya beans are a good source, but beans belonging to the legumes are not. See also carnitine.

One of the essential amino acids. See also amino acid.

Description

Methionine (C₅H₁₁NO₂S) is an essential, sulfur-containing amino acid. It is the source of sulfur for numerous compounds in the body, including the amino acids cysteine and taurine. The body uses sulfur to influence hair follicles and promote healthy hair, skin, and nail growth. Sulfur also increases the liver's production of lecithin (which reduces cholesterol), reduces liver fat, protects the kidneys, helps the body to excrete heavy metals, and reduces bladder irritation by regulating the formation of ammonia in the urine. Methionine is a lipotropic—a nutrient that helps prevent fat accumulation in the liver, and usually helps detoxify metabolic wastes and toxins.

S-adenosyl-L-methionine (SAM, or SAMe) is an active compound made from methionine and adenosine triphosphate (ATP), an enzyme found in muscle tissue. SAMe is manufactured within the body and is found in almost every tissue, but it can also be made synthetically. It acts as a methyl donor in a variety of biochemical pathways. Methylation reactions are essential for the detoxification of harmful products of metabolism, and the synthesis of numerous physiological agents including neurotransmitters, cartilage, and glutathione. (Glutathione is a chemical that plays an important role in biological oxidation-reduction processes, and as a coenzyme. It can combine with toxic substances to form water soluble compounds that can be excreted through the kidneys.)

Methionine is considered essential because it cannot be manufactured in the body and must be obtained through diet. This particular amino acid is found only in meat, fish, eggs, and dairy products. Natural and synthetic methionine supplements are available, as well as supplements containing SAMe.

General Use

Acetaminophen Overdose

Methionine is used to treat acetaminophen (paracetamol) poisoning to prevent liver damage. Preparations containing both methionine and acetaminophen have been formulated for use in situations where overdose may occur.

Arthritis

Most people with arthritis rely on continuous doses of non-steroidal, anti-inflammatory drugs (NSAIDs) like ibuprofen, aspirin, and naproxen for pain relief. SAMe has several advantages over these standard painkillers. It provides effective pain relief and has fewer side effects than these drugs. SAMe also meets with a higher rate of tolerance than other drugs, which is a significant issue for arthritis sufferers. While NSAIDs can cause gastrointestinal bleeding, SAMe can protect against injury to the stomach. Another advantage is that SAMe may actually have a protective effect on joints and even repair cartilage.

Depression

SAMe is beneficial for most forms of depression. In Europe, SAMe is prescribed more often than any other type of antidepressant. Many studies have shown SAMe to be as effective as other antidepressant drugs. It works more quickly and has fewer side effects. SAMe may boost the activity of several brain chemicals involved in mood, such as norepinephrine, dopamine, and serotonin.

Liver Function

Methionine levels help determine the liver's concentration of sulfur-containing compounds and SAMe improves and normalizes liver function. SAMe is used in Europe in the treatment of cirrhosis and damage caused by alcohol. It is essential for the production of glutathione. Methionine itself has a protective effect on glutathione and prevents depletion during toxic overload, which can protect the liver from the damaging effects of toxic compounds.

Through methylation, SAMe is able to inactivate estrogens to prevent estrogen-induced cholestasis (suppressed bile flow) in pregnant women and those on oral contraceptives. It also increases membrane fluidity, restoring several factors that promote bile flow. Treatment with SAMe can also help decrease serum bilirubin (pigment in the blood that can cause jaundice) in patients with Gilbert's syndrome, a condition characterized by a chronically elevated serum bilirubin level.

Neurological Disorders

SAMe improves the binding of neurotransmitters to receptor sites in the brain. It is essential for the regeneration of neuron axons following injury, and for the formation of myelin sheaths (a fatty substance) that surround axons. Alzheimer's and Parkinson's patients have very low levels of SAMe, and methionine may help treat some symptoms of Parkinson's disease.

Persons with AIDS have low levels of methionine, which may explain some of the nervous system deterioration that can occur to cause symptoms including dementia. Methionine may improve memory recall in persons with AIDS-related nervous system degeneration, and SAMe may be used in the treatment of HIV-related motor and sensory changes in the extremities.

Low levels of methionine in pregnant women are related to an increased risk of neural tube defects (NTDs) in the fetus. Neural tube defects are caused by the failure of the neural tube to close properly during the formation of the central nervous system in the developing embryo. Mothers whose methionine intake is adequate during the period from three months prior to conception through the first trimester of pregnancy have a significantly lowered risk of having a baby with a neural tube defect.

Other Uses

In Europe, SAMe has been used in clinical studies to treat anxiety, schizophrenia, demyelination diseases, and dementia. Oral doses of methionine have also been given to lower urinary pH and to help in the treatment of liver disorders. SAMe's ability to inactivate estrogens supports the use of methionine in conditions of presumed estrogen excess such as PMS. Methionine in combination with several antioxidants may reduce pain and recurrences of attacks of pancreatitis (inflammation of the pancreas). SAMe also improves the symptoms of fibromyalgia patients, who suffer from chronic muscle pain, non-restorative sleep, and profound fatigue.

As of 2002, cancer researchers are studying the role of methionine in a special diet for patients diagnosed with colon cancer.

Preparations

Amino acid requirements vary according to body weight. Most average-size adults require approximately 800–1,000 mg of methionine per day. Infants require five times that amount, and children need twice that amount. Dosage rates of SAMe for conditions such as depression, fibromyalgia, liver ailments, migraines, and osteoarthritis are 200–400 mg, two or three times per day. Before taking SAMe supplementation, a physician or qualified health practitioner should be consulted.

The usual oral dose of methionine for acetaminophen poisoning is 2.5 g every four hours for four doses starting less than 10–12 hours after acetaminophen ingestion. It may also be given intravenously.

Precautions

Homocysteine is an amino acid that the liver produces after ingesting methionine. Increased methionine intake, in the presence of inadequate intake of folic acid, vitamin B₆, and vitamin B₁₂, may increase the homocysteine in the blood and increase the risk of heart disease, or stroke. A doctor should be consulted to determine if any nutrient supplementation is needed.

Homocystine is the amino acid formed by the oxidation of homocysteine; homocystinuria is an inherited disorder in which there is excess homocystine in the plasma that is excreted in the urine. People with homocystinuria may benefit from a diet low in methionine, and should consult a physician before taking a supplement.

Patients with acidosis (condition of increased acidity in body fluids) or established liver insufficiency should not take methionine, and it should be used with caution in patients with severe liver disease.

A person who is already taking prescription medications for depression should not attempt to take SAMe, since it increases the efficiency of these medications. Those suffering from bipolar (manic-depressive) disorders should not take SAMe, since its antidepressant properties may induce or heighten the manic phase of this condition.

Women who are healthy and eat a well-balanced diet do not require methionine supplementation during pregnancy or while breastfeeding. They should talk to their doctors before using any kind of supplement.

Side Effects

There appears to be no toxic dosage of methionine, but it may cause nausea, vomiting, drowsiness, and irritability. Supplementation of up to 2 g methionine daily for long periods of time has not produced any serious side effects.

Interactions

There are no well-known drug interactions with methionine.

Resources

Books

Brown, Richard, Carol Colman, and Teodoro Bottiglieri. Stop Depression Now. New York: Putnam Publishing Group, 1999.

Periodicals

Baldessarini, R. J. "Neuropharmacology of S-adenosyl-L-methionine." American Journal of Medicine 83 (1987): 95–103.

Carney, M. W., T. K. Chary, T. Bottiglieri, and E. H. Reynolds. "The Switch Mechanism and the Bipolar/Unipolar Dichotomy." British Journal of Psychiatry 154 (1989):48-51.

Fuchs, Charles S. "Optimizing the Diet for Colon Cancer Therapy and Survival." Journal of Nutrition 131 (November 2001): 3131S.

Shoob, Hylan D., Roger G. Sargent, Shirley J. Thompson, et al. "Dietary Methionine is Involved in the Etiology of Neural Tube Defect-related Pregnancies in Gumans." Journal of Nutrition 131 (October 2001): 2653.

[Article by: Melissa C. McDade; Rebecca J. Frey, PhD]

For more information on methionine, visit Britannica.com.

Met; a sulfur-containing amino acid occurring in proteins, which is an essential component of the diet of animals.

• m. deficiency — exacerbates deficiencies of choline and vitamin B₁₂.
• m. enkephalin — met-enkephalin; see enkephalin.
• m. sulfoximine — the convulsant agent produced in flour by the agene process. Causes hysteria in dogs, ferrets, rabbits and cats, but other species are not affected.

Methionine
IUPAC name	Methionine
Other names	2-amino-4-(methylthio)butanoic acid
Identifiers
Abbreviations	Met, M
CAS number	59-51-8 Y, 63-68-3 (L-isomer) 348-67-4 (D-isomer)
PubChem	876
EC-number	200-432-1
ATC code	V03AB26,QA05BA90, QG04BA90
SMILES	CSCC[C@H](N)C(O)=O
InChI	1/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)
ChemSpider ID	853
Properties[1]
Molecular formula	C5H11NO2S
Molar mass	149.21 g mol−1
Appearance	white crystalline powder
Density	1.340 g/cm3
Melting point	281 ºC decomp.
Solubility in water	soluble
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Methionine (pronounced /mɛˈθaɪ.ɵniːn, mɛˈθaɪ.ɵnɪn/; abbreviated as Met or M)^[2] is an α-amino acid with the chemical formula HO₂CCH(NH₂)CH₂CH₂SCH₃. This essential amino acid is classified as nonpolar.

Contents 1 Function 2 Betaines 3 Biosynthesis 4 Other biochemical pathways 4.1 Generation of homocysteine 4.2 Regeneration of methionine 4.3 Conversion to cysteine 5 Synthesis 6 Dietary aspects 7 See also 8 References 9 External links

Function

Together with cysteine, methionine is one of two sulfur-containing proteinogenic amino acids. Its derivative S-adenosyl methionine (SAM) serves as a methyl donor. Methionine is an intermediate in the biosynthesis of cysteine, carnitine, taurine, lecithin, phosphatidylcholine, and other phospholipids. Improper conversion of methionine can lead to atherosclerosis.

This amino acid is also used by plants for synthesis of ethylene. The process is known as the Yang Cycle or the methionine cycle.

Methionine is one of only two amino acids encoded by a single codon (AUG) in the standard genetic code (tryptophan, encoded by UGG, is the other). The codon AUG is also the "Start" message for a ribosome that signals the initiation of protein translation from mRNA. As a consequence, methionine is incorporated into the N-terminal position of all proteins in eukaryotes and archaea during translation, although it is usually removed by post-translational modification.

Betaines

(S)-Methionine (left) and (R)-methionine (right) in zwitterionic form at neutral pH

Biosynthesis

As an essential amino acid, methionine is not synthesized in humans, hence we must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine is synthesized via a pathway that uses both aspartic acid and cysteine. First, aspartic acid is converted via β-aspartyl-semialdehyde into homoserine, introducing the pair of contiguous methylene groups. Homoserine converts to O-succinyl homoserine, which then reacts with cysteine to produce cystathionine, which is cleaved to yield homocysteine. Subsequent methylation of the thiol group by folates affords methionine. Both cystathionine-γ-synthase and cystathionine-β-lyase require Pyridoxyl-5'-phosphate as a cofactor, whereas homocysteine methyltransferase requires Vitamin B12 as a cofactor.^[3]

Enzymes involved in methionine biosynthesis:

1. aspartokinase
2. β-aspartate semialdehyde dehydrogenase
3. homoserine dehydrogenase
4. homoserine acyltransferase
5. cystathionine-γ-synthase
6. cystathionine-β-lyase
7. methionine synthase (in mammals, this step is performed by homocysteine methyltransferase)

Methionine biosynthesis

Other biochemical pathways

Fates of methionine

Although mammals cannot synthesize methionine, they can still utilize it in a variety of biochemical pathways:

Generation of homocysteine

Methionine is converted to S-adenosylmethionine (SAM) by (1) methionine adenosyltransferase.

SAM serves as a methyl-donor in many (2) methyltransferase reactions and is converted to S-adenosylhomocysteine (SAH).

(3) adenosylhomocysteinase converts SAH to homocysteine.

There are two fates of homocysteine: it can be used to regenerate methionine, or to form cysteine.

Regeneration of methionine

Methionine can be regenerated from homocysteine via (4) methionine synthase.

It can also be remethylated using glycine betaine (NNN-trimethyl glycine) to methionine via the enzyme Betaine-homocysteine methyltransferase (E.C.2.1.1.5, BHMT). BHMT makes up to 1.5% of all the soluble protein of the liver, and recent evidence suggests that it may have a greater influence on methionine and homocysteine homeostasis than methionine synthase.

Conversion to cysteine

Homocysteine can be converted to cysteine.

• (5) Cystathionine-β-synthase (a PLP-dependent enzyme) combines homocysteine and serine to produce cystathionine. Instead of degrading cystathionine via cystathionine-β-lyase, as in the biosynthetic pathway, cystathionine is broken down to cysteine and α-ketobutyrate via (6) cystathionine-γ-lyase.
• (7) α-ketoacid dehydrogenase converts α-ketobutyrate to propionyl-CoA, which is metabolized to succinyl-CoA in a three-step process (see propionyl-CoA for pathway).

Synthesis

Racemic methionine can be synthesized from diethyl sodium phthalimidomalonate by alkylation with chloroethylmethylsulfide (ClCH₂CH₂SCH₃) followed by hydrolysis and decarboxylation.^[4]

Dietary aspects

Food sources of Methionine^[5]

Food	g/100g
Sesame seeds flour (low fat)	1.656
Brazilnuts	1.008
Soy protein concentrate	0.814
Wheat germ	0.456
Oat	0.312
Peanuts	0.309
Chickpea	0.253
Corn, yellow	0.197
Almonds	0.151
Beans, pinto, cooked	0.117
Lentils, cooked	0.077
Rice, brown, medium-grain, cooked	0.052

High levels of methionine can be found in sesame seeds, Brazil nuts, fish, meats and some other plant seeds. Most fruits and vegetables contain very little of it. Most legumes are also low in methionine.

Racemic methionine is sometimes added as an ingredient to pet foods.^[6]

Methionine restriction without energy restriction extends mouse lifespan.^[7]

See also

• Allantoin
• Formylmethionine
• Paracetamol_poisoning#Treatment - A Methionine-Paracetamol preparation that might prevent hepatotoxicity.
• Photo-reactive methionine

References

1. ^ Weast, Robert C., ed. (1981), CRC Handbook of Chemistry and Physics (62nd ed.), Boca Raton, FL: CRC Press, p. C-374, ISBN 0-8493-0462-8 .
2. ^ "Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Recommendations 1983)", Pure Appl. Chem. 56 (5): 595–624, 1984, doi:10.1351/pac198456050595 .
3. ^ Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000), Principles of Biochemistry (3rd ed.), New York: W. H. Freeman, ISBN 1-57259-153-6 .
4. ^ Barger, G.; Weichselbaum, T. E. (1934), "dl-Methionine", Org. Synth. 14: 58, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=CV2P0384 ; Coll. Vol. 2: 384 .
5. ^ National Nutrient Database for Standard Reference, U.S. Department of Agriculture, http://www.nal.usda.gov/fnic/foodcomp/search/, retrieved 2009-09-07 .
6. ^ What's in your dog's food?, Ojibwa Yorkies, http://www.yorkshire-terrier.com/dogfood.htm, retrieved 2009-09-07 .
7. ^ Miller, Richard A.; Buehner, Gretchen; Chang, Yayi; Harper, James M.; Sigler, Robert; Smith-Wheelock, Michael (2005), "Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance", Aging cell 4 (3): 119–125, doi:10.1111/j.1474-9726.2005.00152.x, PMID 15924568 .

External links

• Foods containing methionine
• Computational Chemistry Wiki

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